Targeting non-invasive treatment for cardiac amyloidosis

Years ago, as a University of Toronto nursing student in the cardiovascular and vascular surgery unit of the Peter Munk Cardiac Centre, Natalie Galant watched a lot of patients and families going through trying times.

“Having frontline experience really awakened me to areas of research that need more attention,” Galant said. “I wanted to make more of an impact.”

The aspiring medical researcher won a 2015 Education Fund award from the Ted Rogers Centre for Heart Research – for her work in uncovering how an innovative and specific type of immunotherapy could treat or prevent the progression of heart disease. It involves a collaboration between University Health Network, University of Toronto and a U.S. pharmaceutical company.

Transthyretin (TTR) is a protein in the blood that carries thyroid hormones T3 and T4, as well as vitamin A, but it runs the risk of misfolding and triggering cardiac amyloidosis – plaque buildup on the heart. The resulting heart dysfunction can be lethal. TTR-related cardiac amyloidosis is highly underdiagnosed despite affecting a wide variety of people, including 25% of men over 80.

Radically new era of heart research

At present, the main treatment is surgery but many aging patients aren’t eligible for a transplant. Galant has helped develop an antibody that might provide one very significant solution. The antibody targets the problem – the misfolded protein – while leaving the healthy protein alone so it doesn’t disrupt vitamin A and thyroid levels. This antibody has been found to attach to TTR’s inner surface and, together with the immune system, prevents the buildup of disease-causing plaque.

“This project allows me to help with the pioneering and expansion of a radically new area of heart research within the medical sciences,” Galant said. “To treat cardiac amyloidosis would be huge.”

As for now, pre-clinical studies are nearing completion and Galant and others are setting forth trying to figure out exactly how these antibodies prevent plaque build-up. The goal would be an immunotherapeutic drug that would act solely on the misfolded protein, providing a truly novel treatment option.

Her supervisor is U of T professor Avi Chakrabartty. “Natalie’s project is a prime example of how modern medical research is an intricate collaborative effort involving industry, university, and hospital research institutes,” he said.